Aldosterone has been implicated in the regulation of transport in the thick ascending limb of Henle (TALH) and along the collecting tubule. The evidence is strongest for an action on Na and K transport in the cortical collecting tubule (CCT) and H secretion in the inner stripe of the outer MCD. Its director or indirect role in the TALH and other possible targets like the connecting tubule remain elusive. In the adrenalectomized rabbit, effects of aldosterone on Na, K and H are relatively rapid, with appreciable stimulation of these processes being demonstrated within 1-3 hours after in vivo administration. On the other hand, within 30-60 minutes after application in vitro, prostaglandins (PGs) can rapidly inhibit solute reabsorption in the TALH and CCT, thus modulating the actions of steroid. Recovery from prostaglandin inhibition is also acute. Prostaglandin synthesis is enhanced under a variety of conditions, including hypokalemia and a rise in renal interstitial pressure, the latter associated with "escape" from mineralocorticoid action, or that physiological adaptation that allows release from the Na-retaining properties of the steroid. Major sites of PG synthesis include those collecting duct sites regulated by aldosterone as well as the interstitial cells surrounding the TALH. Part of the mechanism of action of aldosterone on solute transport appears to involve stimulation f NaK ATPase by an amiloride and thus probably a Na-sensitive process. Experiments from our laboratory have suggested that part of the mechanism of action of prostaglandins may involve acute suppression of apparent NaK ATPase activity. Recent results have also suggested that NaK ATPase may be under short-term control of G-proteins by an Na-dependent pathway. The present study therefore attempts to determine the mechanism and nephron site of action of steroids and prostaglandins, and whether they modulate NaK ATPase activity and in some circumstances, a K ATPase activity. These studies should provide information about the short-term regulation of Na reabsorption by the distal nephron and the physiological role of PGs in models of escape and K adaptation.